Chronic renal insufficiency progresses to end-stage renal failure in patients, just as it does after renal ablation in animals. Most patients with glomerular filtration rates below about 25 ml per minute will eventually require dialysis or transplantation, regardless of the original cause of reduced function. Time plots of the reciprocal of serum creatinine concentration suggest steady deterioration of nephron function at rates peculiar to each patient but not characteristic of the underlying disease. Pathological studies in diverse forms of human renal disease have revealed hypertrophy (presumably reflecting hyperfiltration) of the nephron units least damaged by the original disease process. These observations, coupled with results in animals, suggest that the increased pressures and flows acting on remnant glomerular capillaries may be responsible for progression of renal failure after an initial insult has reduced nephron mass. Such elevations in glomerular pressures and flows in remnant kidneys of animals can be prevented by dietary protein restriction. Furthermore, dietary protein restriction, both with and without amino acid supplements or keto-acid analogues of esssential amino acid, has been shown to be effective in preserving renal function in several recent studies involving small numbers of patients followed in most cases for relatively short periods of time. Accordingly, the aims of this proposal are: 1) to determine the prolonged effects of different protein-restricted diets on the progression of chronic renal failure. We will compare a self-selected diet containing unlimited protein with each of the following protein-restricted diets: (a) approximately 0.6 g protein/kg/day or 20 g protein/day supplemented with (b) essential amino acids or (c) ketoacids; 2) to determine compliance with protein-restricted diets; 3) to determine whether nutrition is adequate during long-term therapy with protein-restricted diets; 4) to determine whether reducing dietary protein alters estimates of glomerular plasma flow and hydraulic pressure in patients with chronic renal failure; 5) to determine if the kidneys of patients with chronic renal failure respond to a single high-protein meal with an abrupt increase in renal blood flow and GFR; and 6) to determine the effect of protein-restricted diet on the course of patients who subsequently undergo dialysis and transplantation.